Drug interactions
Methadone + Paroxetine
Severity: Moderate
Methadone and Paroxetine: moderate interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Paroxetine inhibits CYP2D6, which can modestly raise levels of the R-methadone enantiomer, and both drugs have some QT prolonging potential. This can increase methadone effects, sedation and arrhythmia risk, and serotonergic effects are also possible.
What this interaction means in plain words
Methadone and Paroxetine can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Methadone belongs to Musculoskeletal; Paroxetine belongs to Central Nervous System.
Why it happens
CYP2D6 inhibition by paroxetine raises methadone exposure, with additive QT effects and serotonergic activity.
What to do
Monitor for sedation and opioid excess when paroxetine is started, and consider an ECG in patients with other QT risk factors. Adjust the methadone dose if needed and watch for signs of serotonin toxicity.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Methadone
- Alvimopan + Methadone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Methadone Contraindicated
- Droperidol + Methadone Contraindicated
- Ibutilide + Methadone Contraindicated
- Isocarboxazid + Methadone Contraindicated
- Lefamulin + Methadone Contraindicated
Other interactions of Paroxetine
- Isocarboxazid + Paroxetine Contraindicated
- Methylene blue + Paroxetine Contraindicated
- Paroxetine + Phenelzine Contraindicated
- Paroxetine + Pimozide Contraindicated
- Paroxetine + Procarbazine Contraindicated
- Paroxetine + Selegiline Contraindicated
Frequently asked questions
Can I take Methadone with Paroxetine?
MediHelp rates the interaction as moderate. Methadone and Paroxetine can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Paroxetine inhibits CYP2D6, which can modestly raise levels of the R-methadone enantiomer, and both drugs have some QT prolonging potential. This can increase methadone effects, sedation and arrhythmia risk, and serotonergic effects are also possible.
How serious is the interaction between Methadone and Paroxetine?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for sedation and opioid excess when paroxetine is started, and consider an ECG in patients with other QT risk factors. Adjust the methadone dose if needed and watch for signs of serotonin toxicity.
What other medicines interact with Methadone?
MediHelp also lists interactions of Methadone with, for example, Alvimopan, Calcium / magnesium / potassium / sodium oxybates, Droperidol. The full list is on the Methadone page.
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